2,5-Dichloro-1-(3{40 -chloro-2{40 -butenyloxy)-benzene

ABSTRACT

A novel compound of the formula   IN THE FORM OF ITS E isomer or Z isomer or mixtures thereof which is useful as an additive to domestic animal feed, particularly for cattle and fowl.

United States Patent [191 Grandadam 2,5-DICHLORO-l-(3 '-CHLORO-2'- BUTENYLOXY)-BENZENE [75] Inventor: Jean Andre Grandadam, Saint-Maur des Fosses, France [73] Assignee: Roussel Uclaf, Paris, France [22] Filed: Apr. 17, 1973 [21] App]. No.: 351,828

[30] Foreign Application Priority Data Apr. 21, 1972 France 72.14117 [52] US. Cl 260/612 R; 424/340 [51] Int. Cl C07c 43/14; C07c 43/20 [58] Field of Search 260/612 R July 15, 1975 USSR, Vol. 5, p. 1479 (1969).

Primary Examiner-Donald G. Daus Assistant ExaminerD. B. Springer Attorney, Agent, or Firm-Hammond & Littell [57] ABSTRACT A novel compound of the formula in the form of its E isomer or Z isomer or mixtures thereof which is useful as an additive to domestic animal feed, particularly for cattle and fowl.

4 Claims, No Drawings 2,5-DICHLORO-l-(3 -CHLORO-2 -BUTENYLOXY)- BENZENE OBJECTS OF THE INVENTION THE INVENTION The novel ether of the invention is 2,5-dichloro-l- (3'-chloro-2'-butenyloxy)-benzene of the formula in the form of its E or Z isomers or mixtures thereof. The said compound may be prepared by condensing 2,5-dichlorophenol with a l-halo-3-chloro-2-butene in the presence of a basic agent to form the compound of formula I in the form of a mixture of its E and Z isomers which can then be separated by known physical methods. Preferably, 2,5-dichlorophenol is condensed with 1,3-dichloro-2-butene or l-iodo-3-chloro-2-butene in the presence of an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide. The separation of the E and Z isomers may be effected by chromatography.

Incorporation of the product into animal feed permits a better feed assimilation which advantageous property causes the animal to rapidly increase in weight. Besides, during the slaughter, it is verified that the weight of the carcasses was significantly more elevated and the classification of the carcasses was clearly better than those of the control animals. The end of the carcass design is the total weight of the animal after slaughter and removal of the viscera and phanera.

It can be concluded that the incorporation of the compounds of formula I into animal feed contributes not only to the increase in the animal weight but also increases the quality of the meat. This qualitative and quantitative increase is appreciated both by the average daily weight gain and the consummation indice. This represents the ratio between the amount of feed ingested by the animals and holding the weight of the animal.

The novel animalfeed compositions of the invention are comprised of an anabolisant effective amount of a compound of formula I in association with a nutritive mixture adapted to feed growing animals. The nutritive mixture can be varied according to theanimal to be fed. For the raising of pigs, the feed compositions contain proteins such as soya bean, press cake, meat flour or protein hydrolysates, lipids such as copra press cake or arachide, of carbohydrates such as molasses, of cellulosein the form of bran, of branlor of alfalfa flour and mineral salts. I I ...1

For the raising of poultry; the feed compositionscontain for example cereals, rice hulls, cellulose'and "protein enriched flours. The feed compositions generally contain 50 to 500 ppm of the ether of formula I,'prefer-' ably to 200 ppm for good results. In orderto prepare" the feed compositions containing the active compound of formula I, it is advantageous to prepare first'a-m'o're concentrated mixture containing 2 to 10%, for'exam- 1 1 ple, of the ether of formula I and an inert solid or liquid vehicle. The concentrated mixture can then be added to the feed of the domestic animals in a'suffic'ie'nt amount to obtain a final concentration of 50 to 50 0 ppm of the ether of formula I. I

In a modificationof the invention, the ether of formula I is added to a veterinary medicine used to treat sick or ill animals which generally is due to frequent epizooties in industrial raisings. This permits amelioration generally and therefore obtains qualitative and quantitative results realized with other animals being raised. It can be estimated that the ethers of formula I t can be prepared to be administered to sicloanimals which contribute to restoring or modifying the functions of the organism. J The compositions can be used to increase the due to microbial or parasitaric infections. Itis particularly convenient to improve the general state of farmv yard animals subject to coccidiosis such as chickens,

turkeys or ducks. They may be administered by addition to feeds or in the form of specially prepared compositions. 1

The novel method of the invention for increasing the weight of domesticanimals comprises feeding domestic animals with an anabolisanteffective amount of at least EXAMPLE 1 2,5-dichlorol 3 -chloro-2'-butenyloxy )-benzene 40.75 g of 2,5-dichlorophenol were added to a solution of 16 g of potassium hydroxide pellets in 150 ml of ethanol and then 31.25 g of 1,3-dichloro-2-butene were added thereto. The mixture was refluxed for 6 hours under a nitrogen atmosphere and with stirring and the mixture was filtered. The filtrate was concentrated to ml under reduced pressure and after the addition of water and ice, the mixture was extracted with ether. The ether phase was washed with 0.1 N sodium hydroxide, then with water until the wash waters were neutral, dried over sodium sulfate and evaporated to dryness under reduced pressure to'obtain 59 g of 2,- 5-dichloro-l-( 3-chloro-2-butenyloxy):benzene in the form of an oil which crystallized as colorless needles melting at 2730C. The product was soluble in chlorofor m, ethanol, methanol and acetone and insoluble in water. 4 Q Analysis: 0, 11,0 0; molecular weight: 251.54 Calculated: %C 47.75 %H 3.60 %CI 42.30

holding I of weight or the appetite of sick animals notably those Found: 47.9 3.7 42.1

The saidproduct was a mixture of the E and Z isomers with being isomer E and 90% being isomer Z. For separation, the raw product was chromatographed over silica and eluted with petroleum ether (Boiling point 3570C) to obtain isomer E melting at 35"C and isomer Z melting at 40C.

RMN Spectrum:

CH 129.5130.5 Hz (isomer E) and 128.5l29.5

Hz (isomer Z) CH- 270277 Hz (isomer E) and 280-286 Hz (isomer Z) CI-1z349-356 and 363 Hz (isomer E) and 340-346 and 352 Hz (isomer Z) Aromatic H: 405-440 Hz (isomer E) and 405-440 Hz (isomer Z) The two isomers were colorless solids soluble in most of the usual organic solvents.

EXAMPLE 2 Anaboliant activity of 2,5-dichloro-l-( 3 -ch1oro-2-buteny1oxy)-benzene A. Test on Pigs 1 The anabolisant activity of the product was determined on pigs issuing by cross-breeding Large White Landrace weighing an average 26 kg. The animals were divided into a control group receiving for 43 days only the base feed and a second group receiving for 43 days the base feed containing 100 ppm of the test compound. The base feed consisted of a mixture of barley, of white bran, of small bran, of soya bean press cake, of molasses copra press cake. of meat flour, of dehydrated alfalfa flour and of vitaminized mineral compounds with a percentage of 55% cereal, 25% of cereal refuse. 17% of press cake and 3% of concentrated vitaminized minerals. For the duration of the test (104 days). all the animals received the same feed base. Results:

After about 43 days, the average daily gain increased by 9.5%. In spite of halting the treatment on the 43rd day, this good advantage while diminished was conserved even after about 104 days (5.5%). The classification of the carcasses of the pigs treated with the test product was better than the control animals. During the course of treatment, the consummation indice was improved 4.5% and after 104 days was still maintained at -4%. The data is reported in Tables I and 11.

TABLE 1 Zootechnical Performance in course of falling and slaughter The carcasses were classified in three groups according to quality of meat; group C is the least good; group B is indicative of a good quality meat.

TABLE II Feed Weight Consump- Consumied gain tion Groups in Kg in Kg indice 1st period Control 409.765 4 134.80 3.04 43 days Treated 427.725 147.60 2.90

2nd period Controls 789.835 21 1.40 3.74 61 days Treated 790.825 217.80 3.63

Total Period Controls 1 199.600 346.20 3.47 01 104 days Treated 1218.550 365.40 3.33

B. Test on Chickens The anabolisant activity was determined on male Hubbard chickens with yellow meat in a first test and with I-Iybro chickens with white meat in a second test. The animals were divided into a control group receiving only the base feed and a second group receiving the base feed containing ppm of the test compound. The animals were kept in the test for 48 days and they were 2 weeks old at the start of the test. The results are reported in Tables III and IV.

TABLE 111 HUBBARD CHICKENS Initial Weekly Weight Age in Weekly Gain Weight Consummation in g weeks in g in g Controls Treated Controls Treated Controls:

Treated:

TABLE IV HYBRO CHICKENS Initial Weekly Weight Age in Weekly Gain Weight Consummation in g weeks in g in g Controls Treated Controls Treated Controls:

Treated:

Tables III and IV show that the test product provokes an important anabolisant activity in male chickens at a 5 dose of 100 ppm.

stood that the invention is intended to be limited only 2,5-dichloro-l-(3'-chloro-2'-butenyloxy)-benzene. as defined in the appended claims. 3. A compound of claim 1 which is the Z isomer of I claim: 2,5-dichloro-l-(3'-chloro-2-butenyloxy)-benzene.

l. A compound selected from the group consisting of 4. A compound of claim 1 which is a mixture of the E isomer, Z isomer and mixtures of E and Z isomers of 5 E and Z isomers of 2,5-dichloro-l-(3'-chloro-2- 2,5-dichlorol 3 '-chloro-2 -bute'nyloxy )-benzene. butenyloxy)-benzene.

2. A compound of claim 1 which is the E isomer of 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF E ISOMER, Z ISOMER AND MIXTURES OF E AND Z ISOMERS OF 2,5DICHLORO-1-(3''-CHLORO-2''-BUTENYLOXY)-BENZENE.
 2. A compound of claim 1 which is the E isomer of 2,5-dichloro-1-(3''-chloro-2''-butenyloxy)-benzene.
 3. A compound of claim 1 which is the Z isomer of 2,5-dichloro-1-(3''-chloro-2''-butenyloxy)-benzene.
 4. A compound of claim 1 which is a mixture of the E and Z isomers of 2,5-dichloro-1-(3''-chloro-2''-butenyloxy)-benzene. 